TY - JOUR
T1 - Environmental signals rather than layered ontogeny imprint the function of type 2 conventional dendritic cells in young and adult mice
AU - Papaioannou, Nikos E.
AU - Salei, Natallia
AU - Rambichler, Stephan
AU - Ravi, Kaushikk
AU - Popovic, Jelena
AU - Küntzel, Vanessa
AU - Lehmann, Christian H. K.
AU - Fiancette, Remi
AU - Salvermoser, Johanna
AU - Gajdasik, Dominika W.
AU - Mettler, Ramona
AU - Messerer, Denise
AU - Carrelha, Joana
AU - Ohnmacht, Caspar
AU - Haller, Dirk
AU - Stumm, Ralf
AU - Straub, Tobias
AU - Jacobsen, Sten Eirik W.
AU - Schulz, Christian
AU - Withers, David R.
AU - Schotta, Gunnar
AU - Dudziak, Diana
AU - Schraml, Barbara U.
N1 - Funding:
Open Access funding enabled and organized by Projekt DEAL.
PY - 2021/1/19
Y1 - 2021/1/19
N2 - Conventional dendritic cells (cDC) are key activators of naive T cells, and can be targeted in adults to induce adaptive immunity, but in early life are considered under-developed or functionally immature. Here we show that, in early life, when the immune system develops, cDC2 exhibit a dual hematopoietic origin and, like other myeloid and lymphoid cells, develop in waves. Developmentally distinct cDC2 in early life, despite being distinguishable by fate mapping, are transcriptionally and functionally similar. cDC2 in early and adult life, however, are exposed to distinct cytokine environments that shape their transcriptional profile and alter their ability to sense pathogens, secrete cytokines and polarize T cells. We further show that cDC2 in early life, despite being distinct from cDC2 in adult life, are functionally competent and can induce T cell responses. Our results thus highlight the potential of harnessing cDC2 for boosting immunity in early life.
AB - Conventional dendritic cells (cDC) are key activators of naive T cells, and can be targeted in adults to induce adaptive immunity, but in early life are considered under-developed or functionally immature. Here we show that, in early life, when the immune system develops, cDC2 exhibit a dual hematopoietic origin and, like other myeloid and lymphoid cells, develop in waves. Developmentally distinct cDC2 in early life, despite being distinguishable by fate mapping, are transcriptionally and functionally similar. cDC2 in early and adult life, however, are exposed to distinct cytokine environments that shape their transcriptional profile and alter their ability to sense pathogens, secrete cytokines and polarize T cells. We further show that cDC2 in early life, despite being distinct from cDC2 in adult life, are functionally competent and can induce T cell responses. Our results thus highlight the potential of harnessing cDC2 for boosting immunity in early life.
KW - Adaptive Immunity/physiology
KW - Age Factors
KW - Animals
KW - Cell Differentiation/genetics
KW - Cell Separation
KW - Cytokines/metabolism
KW - Dendritic Cells/immunology
KW - Female
KW - Flow Cytometry
KW - Gene Expression Regulation, Developmental/immunology
KW - Hematopoietic Stem Cells/physiology
KW - Male
KW - Mice
KW - Mice, Transgenic
KW - Models, Animal
KW - Primary Cell Culture
KW - RNA-Seq
KW - Single-Cell Analysis
KW - T-Lymphocytes/immunology
KW - Transcriptome/immunology
U2 - 10.1038/s41467-020-20659-2
DO - 10.1038/s41467-020-20659-2
M3 - Article
C2 - 33469015
SN - 2041-1723
VL - 12
JO - Nature Communications
JF - Nature Communications
IS - 1
M1 - 464
ER -